Objective: To construct a prognostic model for epithelial to mesenchymal transition (EMT) in clear cell renal cell carcinoma by bioinformatics, and use the model to predict the survival and prognosis of patients with renal clear cell carcinoma. Methods: The gene chip and clinical data of renal clear cell carcinoma from the TCGA database were download, and 72 normal renal tissue samples and 539 renal clear cell carcinoma tissue samples were obtained. Wilcoxon rank-sum test was used for differential analysis to screen renal clear cell carcinoma. Differentially expressed EMT genes were analyzed by GO and KEGG functional enrichment analysis. Single-factor COX regression and LASSO regression were used to screen the differentially expressed EMT genes related to the prognosis of clear cell renal cell carcinoma, and the risk-predicting model was constructed and verified. Results: A total of 93 differential EMT genes were screened in clear cell renal cell carcinoma, 41 differential genes were related to the overall survival rate of patients, and 6 key EMT differential genes were screened for construction a prognostic model of clear cell renal cell carcinoma. The area under the ROC curve of the training set was 0.717(AUC=0.717), the area under the ROC curve of the validation set was 0.771(AUC=0.771). Multivariate COX regression analysis was conducted with risk model and clinical variables (including age, gender, clinical stage). The results showed that the prognostic model could be used as an independent prognostic factor for clear cell renal cell carcinoma (P＜0.001). Conclusion: The constructed and validated EMT prognostic model could be used to predict the prognosis of patients with renal clear cell carcinoma.
ZHONG Wenjie
,
CHEN Changnan
,
LU Honghong
. Establishment and validation of prognostic model for epithelial to mesenchymal transition in clear cell renal cell carcinoma[J]. Journal of Baotou Medical College, 2023
, 39(7)
: 39
-45
.
DOI: 10.16833/j.cnki.jbmc.2023.07.008
[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019[J].CA Cancer J Clin, 2019, 69(1): 7-34.
[3] Kondoh CN, Miura Y, Yamanaka T. Sunitinib alone or after nephrectomy in renal cancer[J].N Engl J Med, 2018, 379(19): 1877.
[4] Hahn AW, Drake C, Denmeade SR, et al. A phase I study of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients with refractory metastatic renal cell carcinoma[J]. Oncologist, 2020, 25(2): 121-e213.
[5] Stein JE, Lipson EJ, Cottrell TR, et al. Pan-tumor pathologic scoring of response to PD-(L)1 blockade[J].Clin Cancer Res, 2020, 26(3): 545-551.
[6] Zhang L, Min W. Bioorthogonal chemical imaging of metabolic changes during epithelial-mesenchymal transition of cancer cells by stimulated Raman scatteringmicroscopy[J]. J Biomed Opt, 2017, 22(10): 1-7.
[7] Jung AR, Jung CH, Noh JK, et al. Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma[J].Sci Rep, 2020, 10(1): 3652.
[8] Seton-Rogers S. Epithelial-mesenchymal transition: Untangling EMT's functions[J].Nat Rev Cancer, 2016, 16(1): 1.
[9] Xiao W, Wang XG, Wang T, et al. Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma[J].Cancer Gene Ther, 2020, 27(5): 330-340.
[10] Ma J, Li M, Chai J, et al. Expression of RSK4, CD44 and MMP-9 is upregulated and positively correlated in metastatic ccRCC[J].Diagn Pathol, 2020, 15(1): 28.
[11] Shen CQ, Liu J, Wang JR, et al. Development and validation of a prognostic immune-associated gene signature in clear cell renal cell carcinoma[J].Int Immunopharmacol, 2020, 81: 106274.
[12] Shou Y, Liu YN, Xu JJ, et al. TIMP1 indicates poor prognosis of renal cell carcinoma and accelerates tumorigenesis via EMT signaling pathway[J].Front Genet, 2022, 13: 648134.
[13] Nishida J, Miyazono K, Ehata S. Decreased TGFBR3/betaglycan expression enhances the metastatic abilities of renal cell carcinoma cells through TGF-β-dependent and -independent mechanisms[J].Oncogene, 2018, 37(16): 2197-2212.
[14] Farha M, Jairath NK, Lawrence TS, et al. Characterization of the tumor immune microenvironment identifies M0 macrophage-enriched cluster as a poor prognostic factor in hepatocellular carcinoma[J]. JCO Clin Cancer Inform, 2020, 4: 1002-1013.
[15] Zhao B, Hui XD, Zeng HR, et al. Sophoridine inhibits the tumour growth of non-small lung cancer by inducing macrophages M1 polarisation via MAPK-Mediated inflammatory pathway[J].Front Oncol, 2021, 11: 634851.
[16] Corral-Jara KF, Rosas da Silva G, Fierro NA, et al. Modeling the Th17 and TREGS paradigm: implications for cancer immunotherapy[J].Front Cell Dev Biol, 2021, 9: 675099.
[17] Miao D, Margolis CA, Gao W, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma[J].Science, 2018, 359(6377): 801-806.
